Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Kidney Cancer article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Synonyms: RCC, hypernephroma, Grawitz' tumour
Renal cell carcinoma (RCC) is the most common of the tumours of the kidney in adults, accounting for over 80% of neoplasms arising from the kidney.In children, Wilms' tumour is the most common. Benign tumours of the kidney are rare. RCC originates from the proximal renal tubular epithelium. Renal cancer occurs in hereditary and non-hereditary forms, both of which are associated with structural alterations of the short arm of chromosome 3 (3p).
RCC can be further subdivided. Most RCCs are clear cell and the other types of RCC are papillary, chromophobe and collecting duct carcinoma.
The other histological types of renal tumours include:
- Transitional cell carcinoma.
- Renal oncocytoma.
- Wilms' tumour.
- Angiomyolipoma - commonly seen in patients with tuberous sclerosis.
- Adenoma - frequently found as an incidental finding at post-mortem; if diagnosed during life, it is treated with partial nephrectomy, due to histological similarity to adenocarcinoma.
- Renal cancers account for approximately 2-3% of all malignancies, with the highest incidence in Western countries.
- Males are more likely to be affected than females, with a ratio of 1.5:1.
- The incidence of kidney cancer begins to rise after the age of 40 and is highest in people aged between 60 and 70 years.
- Several risk factors have been identified, particularly smoking and obesity.
- Approximately 2-3% of RCCs are hereditary and several autosomal dominant syndromes are described, each with a distinct genetic basis and phenotype, the most common one being von Hippel Lindau disease.
- Since the late 1970s, renal cancer incidence rates have more than doubled in the UK. There appear to be several factors and some are preventable, especially smoking and obesity.
- Risk factors include lifestyle, smoking, obesity and hypertension.
- Other risk factors include long-term renal dialysis, tuberous sclerosis, renal transplant recipients and acquired renal cystic disease.
The use of ultrasound and CT scans has increased the detection of asymptomatic RCC. More than 50% of adult renal tumours are detected when using ultrasound to investigate nonspecific features.
- The classic triad of haematuria, loin pain and loin mass is not often seen now.
- Other presentations include fatigue, weight loss, macroscopic haematuria, palpable mass, varicocele, bilateral ankle oedema, pyrexia of unknown origin and hypertension.
- There is often no abnormality on examination.
- 25-30% of patients present with symptoms of metastatic disease - eg, haemoptysis, bone pain or pathological fracture.
- Paraneoplastic symptoms (eg, neuromyopathy, anaemia, polycythaemia, amyloidosis, elevated ESR, hypercalcaemia and abnormal LFTs) are found in approximately 30% of patients.
- Spread is into adjacent structures of the adrenal glands, liver, spleen, colon or pancreas. Local lymph nodes are often involved.
- It may extend into the renal vein and then into the inferior vena cava.
- The lungs are the most common site of metastases. The classical picture of cannon ball secondaries is almost diagnostic.
- It is one of the carcinomas to metastasise to bone where it produces osteolytic lesions.
- Urinalysis, cytology, culture and sensitivity should be performed to exclude urinary tract infection.
- Renal function tests; however, if one kidney is functioning well the renal function should be normal.
- FBC may detect iron-deficiency anaemia (from haematuria) or polycythaemia (some renal tumours produce erythropoietin and increase haematocrit).
- CT renal scanning before and after intravenous contrast is the best initial investigation.MRI or ultrasound scanning may be used if the results are equivocal.
- Enhancements such as multidetector CT 3-dimensional mapping and diffusion-weighted MRI imaging may be helpful to confirm the morphology and identify venous involvement, respectively.
- Intravenous urogram (IVU) may be needed, especially to show any obstruction to flow. IVU is not a good way to search for a clear cell carcinoma.
- Cystoscopy can exclude bladder tumours as a cause of haematuria.
- Renal angiography may possibly be required to assess the blood supply.
- CXR - classical cannon ball secondaries may be seen in the lung. They are discrete circular metastases. Chest CT scan is more sensitive.
- Metastases: skeletal survey or bone scan may be required for bone metastases. A brain CT scan may also be indicated, depending on symptoms.
- Renal biopsy may be indicated - eg, in patients being treated with surveillance or systemic therapy without previous histopathology.
The current consensus is to use the tumour, node and metastasis (TNM) 2010 system, as recommended by the European Guidelines.
- T: primary tumour:
- TX: primary tumour cannot be assessed.
- T0: no evidence of primary tumour.
- T1: tumour <7 cm in greatest dimension, limited to the kidney.
- T1a: tumour <4 cm in greatest dimension, limited to the kidney.
- T1b: tumour >4 cm but not more than 7 cm in greatest dimension.
- T2: tumour >7 cm in greatest dimension, limited to the kidney:
- T2a: tumour >7 cm in greatest dimension but not more than 10 cm.
- T2b: tumours >10 cm limited to the kidney.
- T3: tumour extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia:
- T3a: tumour grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumour invades the perirenal and/or renal sinus (peripelvic) fat but not beyond Gerota's fascia.
- T3b: tumour grossly extends into the vena cava below the diaphragm.
- T3c: tumour grossly extends into vena cava or its wall above the diaphragm or invades the wall of the vena cava.
- T4: tumour invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland).
- N: regional lymph nodes:
- NX: regional lymph nodes cannot be assessed.
- N0: no regional lymph node metastasis.
- N1: metastasis in a single regional lymph node.
- N2: metastasis in more than one regional lymph node.
- M: distant metastasis:
- M0: no distant metastasis.
- M1: distant metastasis.
- Surgery is the basis of treatment, with or without radiotherapy and/or chemotherapy, depending on the stage of the tumour. Radical nephrectomy is no longer the gold standard curative therapy for patients with localised RCC.
- Partial nephrectomy is considered first-line (whenever possible) for patients with a localised tumour less than 7 cm in diameter.
- Laparoscopic surgery may be involved and the National Institute for Health and Care Excellence (NICE) has reported on both laparoscopic nephrectomy and laparoscopic partial nephrectomy.[4, 5]These should be limited to centres with appropriate expertise. Laparoscopic radical nephrectomy has a lower morbidity compared with open surgery.
- Minimally invasive surgery (eg, image-guided percutaneous radiofrequency (RF) ablation, cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound ablation) may be an option for patients not suitable for open or laparoscopic surgery with smaller peripheral tumours. NICE has recommended that percutaneous RF ablation, laparoscopic cryotherapy, percutaneous cryotherapy and irreversible electroporation may be used as options in the treatment of kidney cancer.[6, 7, 8, 9]
- Renal artery embolisation may be used for pre-RF ablation infarction of renal tumours, palliation of unresectable renal malignancy and for renal haemorrhage.
- The adrenal gland can usually be spared, except in the case of a large upper pole tumour in which there is a high risk of adrenal invasion.
- In older patients, the risks of treatment must be weighed against survival rates for the disease.Decision-supporting nomograms have been developed to assist in this respect.
- Tumour nephrectomy is recommended in otherwise fit patients with metastatic disease, combined with interferon alfa (IFN-α).
- Standard chemotherapy is considered ineffective in patients with RCC.
- Immunotherapy - IFN-α or interleukin 2 (ILN-2) can be considered in selected patients with a clear cell subtype histology. Aldesleukin (recombinant ILN-2) is licensed for metastatic RCC but not for patients with poor performance status and more than one organ with metastatic disease sites, and a period of less than 24 months between initial diagnosis of a primary tumour and date of evaluation of treatment.
- Molecular therapy:
- Some drugs with specific molecular targets have shown benefits in the treatment of advanced RCC.[12, 13]
- Sunitinib (a tyrosine kinase inhibitor) is recommended by NICE as first-line treatment for advanced or metastatic RCC in patients who are suitable for immunotherapy (eg, IFN-α 2a), are mobile and are fit enough for light work. Sunitinib inhibits the growth of cancer cells by blocking a group of closely related tyrosine kinase receptors.
- Pazopanib (a tyrosine kinase inhibitor) is recommended by NICE as a first-line treatment option for people with advanced RCC who have not received prior cytokine therapy.
- Everolimus (a protein kinase inhibitor) is not recommended by NICE for the second-line treatment of advanced RCC.
- In August 2009, NICE issued guidance stating that bevacizumab (a monoclonal antibody that inhibits vascular endothelial growth factor), sorafenib and temsirolimus (a protein kinase inhibitor) should no longer be used as first-line treatment for metastatic or advanced disease but may be continued for patients already taking one of these drugs. Sorafenib (an inhibitor of multiple kinases) and sunitinib are not recommended as second-line drug treatments in this group of patients.
- Metastasectomy is recommended where disease is resectable in otherwise fit patients. It should also be performed in patients with residual and resectable metastatic lesions previously responding to immunotherapy, and/or a limited (solitary) lesion.
- Radiotherapy for the treatment of brain metastases (whole brain irradiation or stereotactic approach) and osseous lesions may be helpful as palliative therapy in selected patients.
- Bisphosphonate therapy has been shown to reduce skeletal-related events in patients with bone metastasis due to metastatic RCC.
Paraneoplastic syndromes may develop and include:
- Polycythaemia due to erythropoietin production.
- Hypercalcaemia due to production of a parathormone-like hormone.
- Kidney cancer survival is improving and has increased in the last 40 years in the UK.
- 50% of people diagnosed with kidney cancer in England and Wales survive for ten years or more (2010-11).
- 56% of people diagnosed with kidney cancer in England and Wales survive for five years or more (2010-11).
- 72% of people diagnosed with kidney cancer in England and Wales survive for one year or more (2010-11).
- Kidney cancer survival is higher in men than in women at one year and five years but similar at ten years.
- Kidney cancer survival is highest for people diagnosed aged under 50.
- Around three quarters of people diagnosed aged 15-49 survive their disease for five years or more, compared with less than a third of people diagnosed aged 80 and over.
- When diagnosed with early-stage RCC, more than 80% of people with kidney cancer will survive their disease for five years or more, compared with less than 10% of people when diagnosed with late-stage RCC.
- Indicators for a poorer prognosis for patients with metastatic RCC include low performance status, high serum lactate dehydrogenase (LDH), low haemoglobin, high serum calcium and absence of prior nephrectomy.
- Cigarette smoking remains the major culprit but the incidence of smoking is not rising in parallel with the number of cases of RCC.
- Obesity is increasing in Europe and the USA. Morbid obesity doubles the risk. People who are overweight but not obese are 35% more likely to develop RCC.
- Screening is currently confined to patients who have been identified as having one of the known genetic lineages linked with specific RCC subtypes.
Further reading and references
Guidelines on Urothelial Carcinomas of the Upper Urinary Tract; European Association of Urology (2016)
Kidney cancer statistic; Cancer Research UK
Guidelines on Renal Cell Carcinoma; European Association of Urology (2016)
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (2014)
Laparoscopic nephrectomy (including nephroureterectomy); NICE Interventional Procedure Guidance, August 2005
Percutaneous radiofrequency ablation of renal cancer; NICE Interventional Procedure Guidance, July 2010
Laparoscopic cryotherapy for renal cancer; NICE Interventional Procedure Guidance, August 2011
Percutaneous cryotherapy for renal tumours; NICE Interventional Procedure Guidance, July 2011
Irreversible electroporation for treating renal cancer; NICE Interventional Procedure Guidance, February 2013
Ginat DT, Saad WE, Turba UC; Transcatheter renal artery embolization: clinical applications and techniques. Tech Vasc Interv Radiol. 2009 Dec12(4):224-39.
Kutikov A, Egleston BL, Wong YN, et al; Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram. J Clin Oncol. 2010 Jan 1028(2):311-7. Epub 2009 Nov 23.
Coppin C, Le L, Porzsolt F, et al; Targeted therapy for advanced renal cell carcinoma. Cochrane Database Syst Rev. 2008 Apr 16(2):CD006017.
Rini BI, Campbell SC, Escudier B; Renal cell carcinoma. Lancet. 2009 Mar 28373(9669):1119-32. Epub 2009 Mar 5.
Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma; NICE Technology Appraisal Guidance, March 2009
Pazopanib for the first line treatment of metastatic renal cell carcinoma; NICE Technology Appraisal Guidance, February 2011, updated August 2013.
Everolimus for the second-line treatment of advanced renal cell carcinoma; NICE Technology Appraisal Guidance, April 2011
Bevacizumab (first-line), sorafenib (first- and second-line), sunitinib (second-line) and temsirolimus (first-line) for the treatment of advanced and/or metastatic renal cell carcinoma; NICE Technology Appraisal Guidance, August 2009
Volpe A, Patard JJ; Prognostic factors in renal cell carcinoma. World J Urol. 2010 Jun28(3):319-27. doi: 10.1007/s00345-010-0540-8. Epub 2010 Apr 3.
Wood LS; Renal cell carcinoma: screening, diagnosis, and prognosis. Clin J Oncol Nurs. 2009 Dec13 Suppl:3-7.